Warfarin, 3-.alpha.-phenyl-.beta.-acetylethyl-4-hydroxycoumarin, which has the chemical structure ##STR1##
has, since the 1950s been in use as an active ingredient in rodenticidal compositions. In addition to its use as a rodenticide, warfarin is also used, in generally smaller amounts, in humans to provide similar anti-coagulating effects.
The basis for the effectiveness of warfarin as a rodenticide lies in the fact that it is effective in small, multiple doses. One or two doses of the compound are seldom fatal if taken at the recommended concentration; thus the hazard of acute toxicity to man, domestic animals, and wildlife is greatly reduced. In practical use, warfarin has been sold as a "concentrate" containing 0.5 percent of the active ingredient. This is diluted for use with a suitable bait, to a concentration of about 0.025 percent. Baits commonly used are cereal products, corn meal, rolled oats, mixed animal feeds, and similar products. Baits containing warfarin can be placed in stations and left there for considerable periods of time, so that the rodent populations may partake of several doses in sequence. Usually the rodents begin to die after four or five daily doses of the materials, and the population is greatly reduced or eradicated in approximately three weeks. Death is caused by hemorrhages, brought about by the action of the warfarin in reducing the clotting power of the blood. These hemorrhages may be external or internal and can be initiated by very slight injury or capillary damage. One of the other advantages of warfarin is that, because multiple ingestions are required to kill the rodents, they do not develop bait shyness.
Beginning in 1969, rodents-- particularly rats and, to a somewhat lesser extent, mice-- began showing resistance to warfarin baits. The general assumption was that such resistance had a genetic basis. Similar resistance was found regarding the use of warfarin as an anti-coagulant in treating humans and, to a certain extent, a possible genetic, or at least familial, basis for the decrease in effectiveness of warfarin in treating humans has been substantiated.
As far as warfarin in rodenticides is concerned, the development of resistance has spawned the search for other rodenticidal compounds, including particularly other coumarin derivatives such as flocoumafen, difenacoum and brodifacoum. Brodifacoum currently appears to be the compound of choice in rodenticidal compositions, although others are used. Unfortunately, many of these other compounds also exhibit toxicity toward household pets and therefore use of brodifacoum-containing rodenticidal compositions has to be carefully controlled in a household environment.
As noted above, warfarin, which is often referred to as a "first generation anti-coagulant rodenticide", has the advantage of very low toxicity toward household pets and wildlife and its use does not involve the need to take excessive precautions to avoid contact with household pets or wildlife. Since warfarin has been available for over 40 years and there have been extensive studies of its effectiveness and toxicological properties, it would be extremely advantageous to be able again to use warfarin in commercial rodenticide formulations.